New molecular tool for a quick and easy detection of apple scab in the field

Venturia inaequalis, an agent of apple scab, is the most important pathogen of Malus x domestica. Control measures against this pathogen rely on intensive phytosanitary programs based on predictive models to identify the meteorological conditions conducive to the primary infection. The detection of the pathogen in field, both in naturally infected symptomatic and asymptomatic leaves, is desirable. Loop-mediated isothermal amplification (LAMP) assays are profitable molecular diagnostic tools for the direct detection of pathogens in field. A LAMP assay for V. inaequalis has been designed on the elongation factor 1-alpha sequence. The validation of the LAMP assay was carried out following the international EPPO standard PM 7/98 in terms of specificity, sensitivity, repeatability and reproducibility. Specificity testing was performed using target and non-target species, such as phylogenetically related Venturia species and other pathogens commonly found in apple, resulting in positive amplification only for the target with a time to positive ranging from 20 to 30 min. Sensitivity testing was performed with serial dilutions of DNA of the target and by artificial inoculation of young apple leaves. The reliability of the LAMP assay as an early-detection tool and its user-friendly application make it suitable for the diagnosis of apple scab in the field

Forward precision medicine: Micelles for active targeting driven by peptides

Precision medicine is based on innovative administration methods of active principles. Drug delivery on tissue of interest allows improving the therapeutic index and reducing the side effects. Active targeting by means of drug-encapsulated micelles decorated with targeting bioactive moieties represents a new frontier. Between the bioactive moieties, peptides, for their versatility, easy synthesis and immunogenicity, can be selected to direct a drug toward a considerable number of molecular targets overexpressed on both cancer vasculature and cancer cells. Moreover, short peptide sequences can facilitate cellular intake. This review focuses on micelles achieved by self-assembling or mixing peptide-grafted surfactants or peptide-decorated amphiphilic copolymers. Nanovectors loaded with hydrophobic or hydrophilic cytotoxic drugs or with gene silence sequences and externally functionalized with natural or synthetic peptides are described based on their formulation and in vitro and in vivo behaviors

The discovery of new and more potent chloropyramine (C4) analogues for the potential treatment of invasive breast cancer

Breast cancer is the second most common cancer worldwide, accounting for 25% of all female cancers. Although the survival rate has increased significantly in the past few decades, patients who develop secondary site metastasis as well as those diagnosed with triple negative breast cancer still represent a real unmet medical challenge. Previous studies have shown that chloropyramine (C4) inhibits FAK-VEGFR3 signalling. More recently, C4 is reported to have SASH1 inducing properties. However, C4 exerts its antitumour and antiangiogenic effects at high micromolar concentrations (>100 μm) that would not be compatible with further drug development against invasive breast cancer driven by FAK signalling. In this study, molecular modelling guided structural modifications have been introduced to the chloropyramine C4 scaffold to improve its activity in breast cancer cell lines. Seventeen compounds were designed and synthesized, and their antiproliferative activity was evaluated against three human breast cancer lines (MDA-MB-231, BT474 and T47D). Compound 5c was identified to display an average activity of IC50 = 23.5–31.3 μm, which represents a significant improvement of C4 activity in the same assay model. Molecular modelling and pharmacokinetic studies provided more promising insights into the mechanistic features of this new series

Observation of the Decay B^-→D_s^((*)+)K^-ℓ^-ν̅ _ℓ

We report the observation of the decay B^- → D_s^((*)+)K^-ℓ^-ν̅ _ℓ based on 342  fb^(-1) of data collected at the Υ(4S) resonance with the BABAR detector at the PEP-II e^+e^- storage rings at SLAC. A simultaneous fit to three D_s^+ decay chains is performed to extract the signal yield from measurements of the squared missing mass in the B meson decay. We observe the decay B^- → D_s^((*)+)K^-ℓ^-ν̅ _ℓ with a significance greater than 5 standard deviations (including systematic uncertainties) and measure its branching fraction to be B(B^- → D_s^((*)+)K^-ℓ^-ν̅ _ℓ)=[6.13_(-1.03)^(+1.04)(stat)±0.43(syst)±0.51(B(D_s))]×10^(-4), where the last error reflects the limited knowledge of the D_s branching fractions